Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Thermosensitive cyclotriphosphazene-platinum complex conjugate, its preparation method and anticancer agent containing the same

A technology of cyclotriphosphazene and conjugates, which is applied in the field of cyclotriphosphazene-platinum composite conjugates, and can solve the problems of high price, low anticancer activity and limited use

Inactive Publication Date: 2005-04-06
KOREA INST OF SCI & TECH
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to its high toxicity (LD 50 =13mg / Kg, M.J.Cleare, biochemistry (Biochimie) 60,835 (1978)), make its use restricted
Although the second-generation anticancer agent carboplatin showed much lower toxicity than cisplatin (LD 50 =180mg / Kg, M.J.Cleare, Biochemistry 60,835(1978)), but because its anticancer activity is lower than cisplatin, and its price is more expensive than cisplatin, it is not widely used

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Thermosensitive cyclotriphosphazene-platinum complex conjugate, its preparation method and anticancer agent containing the same
  • Thermosensitive cyclotriphosphazene-platinum complex conjugate, its preparation method and anticancer agent containing the same
  • Thermosensitive cyclotriphosphazene-platinum complex conjugate, its preparation method and anticancer agent containing the same

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0031] The preparation method of the present invention can be represented graphically by the following reaction scheme 1:

[0032] Reaction scheme 1

[0033]

Embodiment 1

[0038] {NP[(OCH 2 CH 2 ) 2 OCH 3 ][L-Asp·Pt(dmpda)] 3 preparation of

[0039] Will {NP[(OCH 2 CH 2 ) 2 OCH 3 ][NHCH(CH 2 COOC 2 h 5 )COOC 2h 5 ]} 3 (1.00g, 0.95mmol) was dissolved in methanol (50ml), and the temperature of the reaction vessel was controlled at 0-5°C with an ice-water bath. Slowly add the solution containing excess Ba(OH) under stirring 2 ·8H 2 O (1.19 g, 3.78 mmol) in methanol. The ice-water bath was removed after 30 minutes, and the reaction was continued for 3 hours. The reaction mixture was concentrated under reduced pressure until only a small amount of solvent remained. Excess ether or hexane was added to the concentrated reaction mixture to cause precipitation of the hydrolyzate. The precipitate thus obtained is redissolved in a small amount of methanol and then reprecipitated by adding excess ether or hexane. After the precipitation process was repeated 2-3 times, the final precipitate was vacuum-dried to obtain 0.99 g of cyclotripho...

Embodiment 2

[0053] {NP[(OCH 2 CH 2 ) 2 OCH 3 ][L-Asp·Pt(dach)]} 3 preparation of

[0054] Use {NP[(OCH 2 CH 2 ) 2 OCH 3 ][NHCH(CH 2 COOC 2 h 5 )COOC 2 h 5 ]} 3 (0.73g, 0.69mmol), Ba(OH) 2 ·8H 2 O (0.87g, 2.76mmol), cyclotriphosphazene-barium salt (0.69g, 0.61mmol), and (dach)PtSO 4 (0.63g, 1.83mmol), obtain the final conjugated product {NP[(OCH 2 CH 2 ) 2 OCH 3 ][L-Asp·Pt(dach)]} 3 (1.05 g, 95.5% yield).

[0055] Molecular formula: C 45 h 87 N 12 o 21 P 3 Pt 3

[0056] Elemental analysis (%): C, 29.01; H, 4.79; N, 9.39; P, 5.01; Pt, 30.95

[0057] Theoretical values: C, 29.85; H, 4.84; N, 9.28; P, 5.13; Pt, 32.33

[0058] Proton NMR spectroscopy (D 2 O, ppm):

[0059] δ1.1-1.4(b, 4H,

[0060] δ1.5.1.7(b, 2H,

[0061] δ2.0-2.2(b, 2H,

[0062] δ2.3-2.5(b, 2H,

[0063] Phosphorus NMR spectroscopy (D 2 O, ppm): δ34-44

[0064] Lower critical solution temperature: 92.0°C.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present invention provides a novel thermosensitive cyclotriphosphazene-platinum complex conjugates represented by Formula (1) wherein m is a repeating unit of poly(alkoxyethylene glycol) selected from the integers 2, 7 and 12; n represents the length of the alkyl chain selected from the integers 0, 1, 2 and 3; x represents the length of the anionic amino acid residue selected from the integers 0 (amino malonic acid derivatives), 1 (aspartic acid derivatives) and 2 (glutamic acid derivatives); A2 is a bidentate chelating diamine selected from the group consisting of 2,2-dimethyl-1,3-propanediamine (dmpda), trans(+ / -)-1,2-diaminocyclohexane (dach) and 1,1-diaminomethylcyclohexane (dmach).

Description

field of invention [0001] The present invention relates to a thermosensitive cyclotriphosphazene-platinum complex conjugate which can be administered systemically or locally and has excellent anticancer activity, a preparation method thereof, and an anticancer agent containing the conjugate as an active component. More particularly, the compound of the present invention is a biodegradable cyclotriphosphazene-platinum complex conjugate exhibiting thermosensitivity in the temperature range including body temperature. Background of the invention [0002] The inventors found that by hexachlorocyclotriphosphazene ((NPCl 2 ) 3 ) derivatives obtained by nucleophilic substitution of chlorine atoms of low or high molecular weight hydrophilic poly(alkoxyethylene glycol) and hydrophobic amino acid esters can show thermosensitivity (Korean Patent Application No. 99-48800). The present inventors succeeded in preparing platinum complexes of these trimer derivatives by introducing (diami...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): A61P35/00A61K31/282C07F9/02C07F9/6593C07F15/00C09K3/00
CPCC07F15/0093C07F9/65815A61P35/00C07F9/02
Inventor 孙莲秀宋秀昶李祥汜
Owner KOREA INST OF SCI & TECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products